PALB2 Mutations Linked To Breast Cancer Risk, Prognosis

Breast cancer patients with a mutation in PALB2 may have poorer survival than those without the biomarker

medwireNews: Mutations in the DNA repair protein PALB2 Gene increase both the risk of breast cancer and the risk of mortality, a study of Polish women suggests.

One of two deleterious mutations in PALB2 – 509_510delGA and 172_175delTTGT – were detected in 0.93% of 12,529 Polish women with  breast cancer compared with just 0.21% of 4702 healthy controls, giving an odds ratio of 4.39.

Moreover, after a median follow-up of 53.9 months, 33% of the patients with a PALB2 mutation had died compared with just 16% of those without. This was a significant difference, with a hazard ratio of 2.27 after adjusting for age at diagnosis, tumour characteristics and chemotherapy received.

Among PALB2 mutation carriers, the adjusted HR for mortality was significantly higher for patients with tumours at least 2 cm in diameter than those with smaller tumours, at 3.09 versus 1.2, with 10-year survival rates of 82.4% versus 32.4%.

And for women with triple-negative disease, the adjusted HR for death for those with a PALB2 mutation was 2.46, with a 10-year survival rate of 37.1% compared with 74.4% for the 281 patients with a BRCA1 mutation and 66.3% for those with neither of the aberrations.

“In view of the high mortality associated with a breast cancer larger than 2.0 cm and a PALB2 mutation, efforts should be made to detect small cancers early, by examination by a doctor, screening mammography, and screening MRI”, recommend Steven Narod, from Women’s College Research Institute in Toronto, Ontario, Canada, and co-authors.

“We believe evidence is sufficient to offer screening for PALB2 mutations to women with familial forms of breast cancer, in addition to screening for BRCA1 and BRCA2”, they add, recommending that a clinical database be established to further investigate the impact of PALB2 mutations.

However, Suzette Delaloge and colleagues, from the Gustave Roussy Institute in Villejuif, France, caution in an accompanying comment that the impact of the functionally related BRCA1 and BRCA2 mutations was initially overstated and later shown not to have an adverse impact on prognosis.

While 10% of the PALB2 carriers had contralateral tumours and 5% had cancers at other sites, the commentators note that more information is required on the patients’ chemotherapy regimens and the associated risk of malignancy.

“Altogether, the information currently available on prognosis of breast cancer in PALB2 carriers does not seem mature enough to prompt specific prevention and treatment recommendations, particularly with respect to preventive surgery”, they say.

“Careful breast surveillance should, however, be recommended, using currently available techniques.”

References

Cybulski C, Kluzniak W, Huzarski Tet al. Clinical outcomes in women with breast cancer and aPALB2mutation: a prospective cohort analysis. Lancet Oncol 2015; Advance online publication 7 May. doi:10.1016/S1470-2045(15)70142-7

Delaloge S Caron O, Feunteun J. Effect of PALB2status on breast cancer precision medicine. Lancet Oncol 2015; Advance online publication 7 May. DOI: http://dx.doi.org/10.1016/S1470-2045(15)70182-8

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